Iordanou Ekaterini, Chandran Rachana R, Yang Yonghua, Essak Mina, Blackstone Nicholas, Jiang Lan
Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
Department of Biological Sciences, Oakland University, Rochester, MI 48309, USA.
Dev Biol. 2014 Sep 1;393(1):93-108. doi: 10.1016/j.ydbio.2014.06.016. Epub 2014 Jun 25.
Tubes with distinct shapes and sizes are critical for the proper function of many tubular organs. Here we describe a unique phenotype caused by the loss of a novel, evolutionarily-conserved, Drosophila Smad-like protein, Expansion. In expansion mutants, unicellular and intracellular tracheal branches develop bubble-like cysts with enlarged apical membranes. Cysts in unicellular tubes are enlargements of the apical lumen, whereas cysts in intracellular tubes are cytoplasmic vacuole-like compartments. The cyst phenotype in expansion mutants is similar to, but weaker than, that observed in double mutants of Drosophila type III receptor tyrosine phosphatases (RPTPs), Ptp4E and Ptp10D. Ptp4E and Ptp10D negatively regulate the receptor tyrosine kinase (RTK) pathways, especially epithelial growth factor receptor (EGFR) and fibroblast growth factor receptor/breathless (FGFR, Btl) signaling to maintain the proper size of unicellular and intracellular tubes. We show Exp genetically interacts with RTK signaling, the downstream targets of RPTPs. Cyst size and number in expansion mutants is enhanced by increased RTK signaling and suppressed by reduced RTK signaling. Genetic interaction studies strongly suggest that Exp negatively regulates RTK (EGFR, Btl) signaling to ensure proper tube sizes. Smad proteins generally function as intermediate components of the transforming growth factor-β (TGF-β, DPP) signaling pathway. However, no obvious genetic interaction between expansion and TGF-β (DPP) signaling was observed. Therefore, Expansion does not function as a typical Smad protein. The expansion phenotype demonstrates a novel role for Smad-like proteins in epithelial tube formation.
具有不同形状和大小的管道对于许多管状器官的正常功能至关重要。在此，我们描述了一种由一种新的、进化上保守的果蝇Smad样蛋白Expansion缺失所导致的独特表型。在expansion突变体中，单细胞和细胞内气管分支会形成带有扩大顶端膜的泡状囊肿。单细胞管道中的囊肿是顶端管腔的扩大，而细胞内管道中的囊肿是细胞质空泡样区室。expansion突变体中的囊肿表型与果蝇III型受体酪氨酸磷酸酶（RPTPs）Ptp4E和Ptp10D的双突变体中观察到的表型相似，但较弱。Ptp4E和Ptp10D负向调节受体酪氨酸激酶（RTK）途径，尤其是上皮生长因子受体（EGFR）和成纤维细胞生长因子受体/呼吸急促（FGFR，Btl）信号传导，以维持单细胞和细胞内管道的适当大小。我们表明Exp在遗传上与RTK信号传导相互作用，RTK信号传导是RPTPs的下游靶点。expansion突变体中囊肿的大小和数量通过增加RTK信号传导而增强，并通过减少RTK信号传导而受到抑制。遗传相互作用研究强烈表明，Exp负向调节RTK（EGFR，Btl）信号传导以确保管道大小合适。Smad蛋白通常作为转化生长因子-β（TGF-β，DPP）信号通路的中间成分发挥作用。然而，未观察到expansion与TGF-β（DPP）信号传导之间有明显的遗传相互作用。因此，Expansion并不作为典型的Smad蛋白发挥作用。expansion表型证明了Smad样蛋白在上皮管道形成中的新作用。
